The therapeutic importance of isoniazid metabolism in elderly patients

This is a study of the role of oxygen free radicals in isoniazid induced toxicity and its implications on the safety of isoniazid containing regimens in elderly patients. During isoniazid metabolism, toxic metabolites are produced which, together with isoniazid, may lead to toxicity by mechanism (s) yet unknown. Understanding the mechanism of toxicity is important for effective management and prevention of isoniazid induced toxicity. Elderly patients take priority for this consideration because isoniazid is more toxic in these people. Consequently, "the therapeutic importance of isoniazid metabolism in elderly patients" was found a suitable title for this work. lsoniazid metabolites; acetylisoniazid, monoacetyl-hydrazine and diacetylhydrazine were synthesized and characterized by thin layer chromatography, high performance liquid chromatography (HPLC), ultra-violet absorption spectra and mass spectrometry. Thereafter, these compounds together with hydrazine were used in the subsequent experiments

Evaluation of Traditional Medicines III: The Mechanism of Immune Modulation by PHELA.

PHELA is a herbal traditional medicine that is under development for use as an immune booster in immune compromised individuals. Therefore, the aim of this study was to determine PHELA’s mechanism of action by observing for changes in cytokine profiles. Four groups of Sprague Dawley rats (n = 8) were treated daily and separately with normal-saline, cyclosporine-A, PHELA-only and PHELA+ cyclosporine-A. Thereafter, 4 animals from each group were sacrificed after 7 and 14 days of treatment. Serum Th1 cytokines (IL-2, IFN-γ and TNF-ά) and Th2 cytokines (IL-4 and IL-10) were measured by ELISA. The concentrations of Th1 cytokines in the PHELA-only treated group were similar to the control group on days 7 and 14. However, the Th1 cytokines were higher in the PHELA+cyclosporine-A treated group compared to cyclosporine-A group, and cyclosporine-A concentrations were similar in both groups. These results show that PHELA did not stimulate Th1 cytokines of a normal immune system but stimulated them when the immune system was suppressed by cyclosporine-A. In conclusion, PHELA is an immune-stimulant to a compromised immune system

EVALUATION OF TRADITIONAL MEDICINES I: IDENTIFICATION OF PHELA USING DIFFERENT CHROMATOGRAPHIC TECHNIQUES

PHELA is a herbal mixture of four African traditional medicinal plants that has been used for decades in wasting conditions and is now being developed by the Medical Research Council (MRC) as an immune booster for patients with compromised immune system. A chromatographic fingerprint of PHELA was needed for quality control purposes. Here, a comprehensive method for fingerprinting of PHELA using different chromatographic techniques is described. It involved extraction of the PHELA by either acidic or a simple ‘salting-out’ method, followed by Thin Layer Chromatography (TLC) analysis and/or preparative Column Chromatography (CC). The products were thereafter analyzed by High Performance Liquid Chromatography with UV-detector (HPLC-UV), HPLC with fluorescence-detector (HPLC-FL) and Gas-Chromatography with a Mass Selective Detector spectrometer (GC¬MSD). The fingerprints were successfully used to differentiate PHELA from another common herbal product made from Hypericum perforatum (St. John’s Wort), thereby illustrating its high potential for use in fingerprinting of PHELA and in differentiating it from other herbal medicines. By validating the different chromatographic techniques on the standardized extraction methods, this approach will enable wide application in quality control of PHELA using acceptable procedures, thereby promoting effective monitoring of the finished product in all countries where it will be used

EVALUATION OF TRADITIONAL MEDICINES II: THE USE OF METABOLITE PEAK-KINETICS

PHELA is a herbal mixture of four African traditional medicinal plants that is under development by the Medical Research Council (MRC) for use as an immune stimulant in immune compromised individuals. Before major in vivo investigations could be conducted, there was a need to establish a plasma marker for concentration monitoring of PHELA. Chromatographic separation was achieved using a C18 RP column (250 mm x 4.6 mm x 5 µm), 70% acetonitrile in water and fluorescent detection. Three groups of rats (n=5) were administered with PHELA (15.4 mg/kg) and one rat from each group was sacrificed at 1, 2, 4, 6 and 8 hours. Surprisingly, on the HPLC analysis, none of the marker peaks of spiked plasma were detectable in the plasma of treated animals. Instead, a new peak was observed at 9.2 minutes, which implied that it was a metabolite of PHELA. Using peak area per unit plasma volume (PK-area/L), the relevant pharmacokinetic parameters were derived. The metabolite’s half-life was 3.47±0.35 hours and reached maximum concentration at 4.67 ± 1.15 hrs. It was estimated that with once daily dosing of PHELA, the concentration at steady state (Css) would be 47.52 ± 5.94 PK-area/L with no drug accumulation (Acc index =.009 ± 0.004). In conclusion, the use of peak area per unit volume to derive pharmacokinetics of unknown compounds (Peak-kinetics) and to confirm ingestion of PHELA were demonstrated with a hope that they may appeal to those experiencing similar problems with monitoring of herbal products of which little is known

Co-administration of fresh grape fruit juice (GFJ) and bergamottin prevented paracetamol induced hepatotoxicity after paracetamol overdose in rats

The aim of this study was to evaluate small doses of known cytochrome P450 enzyme inhibitors, grapefruit juice (GFJ) and one of its components, bergamottin (BGT), for the prevention of paracetamol (PAR)-induced hepatotoxicity after overdose in rats. Six groups of 15 Sprague Dawley (SD) rats each were treated with single oral doses of either saline, PAR only 1725 mg/kg, PAR + GFJ low dose (2 ml) and PAR + GFJ high dose (3 ml), PAR + BGT 0.05 mg/kg (BGT-low) and PAR + BGT 0.22 mg/kg (BGT-high). Thereafter, 5 rats from each group were sacrificed after 24, 48 and 72 h and, on each occasion, blood samples were collected for determination of liver and renal function, full blood count (FBC) and PAR concentration. A piece of liver was sent for histopathology. By 48 h the liver enzymes in the PAR-only group were significantly (P < 0.05) higher than in the PAR + GFJ and PAR + BGT groups, i.e., alanine transaminase (ALT) 837 ± 268 u/L and aspertate transaminase (AST) 1359 ± 405 for PAR only; versus ALT 34 ± 48.8 u/L and AST 238 ± 221 for PAR + GFJ-high; ALT 22 ± 13.9 and AST168 ± 49.6 for PAR + BGT-high; and ALT 52 ± 7.2 u/L and AST 147 ± 153 for the control group. The results correlated with the histopathology findings where livers of the PAR-only group exhibited severe centrilobular and hepatocyte necrosis. In conclusion, GFJ and BGT prevented PAR-induced hepatotoxicity after PAR overdose in rats, and this calls for appropriate observation studies in humans

History of medicine : the Hamilton Naki Clinical Scholarship, 2007-2011

The original publication is available at http://www.samj.org.zaThe Hamilton Naki Scholarship was introduced because of the shortage of qualified academic leaders in South African medical schools, especially for academic clinicians from previously disadvantaged backgrounds. There were only a handful of African academic doctors with a significant published record of scholarship in South Africa. If academic physicians from the whole population were not recruited and trained, South Africa would lose its ability to train high-quality health practitioners. To address these deficiencies, the Netcare Physician Partnerships Trust established a scholarship to produce world-class academics in all medical specialties to teach and conduct research comparable to other parts of the world

The Hamilton Naki Clinical Scholarship, 2007 - 2011

The Hamilton Naki Scholarship was introduced because of the shortage of qualified academic leaders in South African medical schools, especially for academic clinicians from previously disadvantaged backgrounds. There were only a handful of African academic doctors with a significant published record of scholarship in South Africa.http://www.samj.org.z